We have investigated the importance of variations in the degree to which organisms control events to which they are exposed. Emphasis has been placed on the consequences for the organism of exposure to aversive events which it cannot control. We desire to isolate the effects of the uncontrollability of the aversive event rather than the event per se. Thus, the typical experiment compares organisms that have been exposed to the identical physical events, with some having control and others not. We found that exposure to aversive events that cannot be controlled by the subject's responses leads to cognitive-perceptual, motivational, and emotional deficits. For example, organisms exposed to inescapable shocks later do not attempt to escape in a different situation where escape is possible, fail to learn to escape even when they do respond, are less aggressive and dominant, show severe symptoms of stress, etc. These have been called learned helplessness effects. We have developed a theoretical structure called the learned helplessness hypothesis to account for them. These concepts have been applied to a variety of problems of human adaptation, including reactive depression, school failure, aging, crowding, etc. The proposed research involves 3 different directions, but tied together by their relationship to learned helplessness. The first is a continuation of prior experimental-behavioral research designed to explore the limits, nature, and causes of learned helplessness effects. The focus is on the discovery of boundary conditions and the testing of various explanations which have been proposed. The second area is infant-mother separation. Separation from the mother is an unpleasant experience over which the infant has no control. Some of the consequences of separation may be learned helplessness effects. In addition, the long term consequences in adulthood of a single separation in infancy that does not entail social isolation but only separation from the mother are not known. The purpose of the research is to investigate the long term consequences of separation and to study the relationship between separation and learned helplessness. The third topic of investigation will be the neurochemical basis of learned helplessness. We have recently discovered that organisms subjected to manipulations which induce learned helplessness become analgesic, and that this analgesia is reversed by opiate antagonists. This suggests that the endogenous opioids, the enkephalins and endorphins, may be involved.